UCD19 CAR T Therapy in Adults With B-ALL and MRD Positivity in CR1
Trial statusRecruiting
Trial phasePhase 1
Trial typeInterventional
Biological sexAll
Age18+
SponsorUniversity of Colorado, Denver
About this trial
This open-label, single arm Phase 1/1b trial aims to determine the safety and tolerability of anti-CD19 chimeric antigen receptor-expressing (CAR) T cells (UCD19 CAR T) in adults with B-ALL that are in first complete remission with MRD positivity. This trial will enroll 10 patients during Phase 1 for apheresis, treatment with lymphodepleting chemotherapy, and UCD19 CAR T cell infusion. Patients will be assessed for DLTs (within 42 days after CAR T infusion) to determine a maximum tolerated dose (MTD), duration of B cell aplasia, overall response rate (at 1-3-, 6- and 12-months), and overall survival and event free survival (at 12- and 24- months) post UCD19 CAR T infusion.
After the initial dose escalation phase, an additional 12 participants will be enrolled in the dose expansion at the MTD to determine preliminary efficacy.
Eligibility criteria
This trial does not accept healthy volunteersQualifiers
Age: ≥ 18 years of age with no upper age limit
ECOG Performance Status ≤ 2
Confirmed B-cell ALL in first complete morphologic remission
For Ph- ALL: > 0.01% by FACS or > 0 clonal sequences by NGS (clonoSEQ). MRD assessment for eligibility must be at least 28 days after the start of SOC induction therapy. Remission-induction therapy must have consisted of multi-agent chemotherapy (≥ 3 systemic anti-leukemia chemotherapy agents).
Disqualifiers
Previous CAR T therapy.
Relapsed or refractory B-cell acute lymphoblastic leukemia, including patients who have evidence of MRD after having previously documented MRD-negative remission.
Mixed phenotype acute leukemia or Burkitt's lymphoma
Not in hematological remission at time of enrollment (Remission is defined as < 5% blasts)
Trial design
Design model
Sequential
Treatments tested in this trial
CD19 Directed CAR T Cell
DrugThe UCD19 CAR T cells are developed through transfection of autologous peripheral blood mononuclear cells with a lentivirus carrying the DNA that encodes a short chain fragment variable region (scFv) derived from an anti-CD19 monoclonal antibody, among other elements.
Treatment groups
29 Participants
are divided into 1 treatment groupGroup A: UCD19 CAR T InfusionExperimental treatment 1 intervention
Trial outcomes
Primary outcomes
1
Safety of UCD19 CAR T in Adults With B-ALL in first complete remission with MRD Positivity: occurrence and frequency of Adverse Events (AEs)
The occurrence and frequency of Adverse Events will be graded using the National Cancer Institute's (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 grading criteria.
Time frame
Up to 30 days after last day of study participation2
Safety of UCD19 CAR T in Adults With B-ALL in first complete remission with MRD Positivity: occurrence of Dose Limiting Toxicities (DLTs)
Adverse events that are at least possibly related to the UCD19 CAR T cells with onset within the first 42 days following UCD19 CAR T cell infusion and are ≥ Grade 3 in severity will be considered DLTs. With exception to hematological toxicity for subjects with normal, Grade 1 or Grade 2 Hematologic Parameters at baseline (independent of transfusion) and cytopenias NOT due to Bone Marrow Involvement by Disease. However, any Grade 4 hematological toxicity (i.e., neutropenia or thrombocytopenia with the exception of lymphopenia) persisting beyond 42 days after infusion will be considered a DLT unless toxicity is attributed to patient's underlying disease.
Time frame
42 days3
Preliminary efficacy of UCD19 CAR T infusion at the MTD in adult B-ALL patients at first complete remission with MRD positivity
Determine the Relapse Free Survival (RFS) rate post UCD19 CAR T infusion. RFS will be measured from the date of infusion of the UCD19 CAR T product to the time of relapse or death from any cause
Time frame
12 and 24 monthsSecondary outcomes
1
Overall response rate (ORR) at 1, 3, 6, 12, and 24 months post UCD19 CAR T infusion as measured by MRD.
MRD negativity is defined as bone marrow that has no detectable blasts at or above the sensitivity threshold for the particular assay used (approximately 0.01% for FACS-MRD, 0.001% for BCR-ABL qPCR, 0.0001% for IgH/TCR NGS). MRD positivity post UCD19 CAR T infusion is defined as \> 0.01% by FACS or a rising number of \> 0 clonal sequences by NGS (clonoSEQ) at two timepoints at least 2-4 weeks apart in the bone marrow or peripheral blood for Ph- ALL, and either \> 0.01% by FACS, a rising number of \> 0 clonal sequences by NGS (clonoSEQ), or less than complete molecular remission (undetectable BCR-ABL1 transcripts by quantitative PCR assay with sensitivity of at least 1 in 100,000) at two timepoints at least 2-4 weeks apart in the bone marrow or peripheral blood for Ph+ ALL.
Time frame
1, 3, 6, 12, and 24 months2
Overall Survival (OS) at 12 and 24 months post UCD19 CAR T infusion.
OS defined as measured from the date of infusion to the time of death from any cause.
Time frame
12 and 24 months3
Event Free Survival (EFS) at 12 and 24 months post UCD19 CAR T infusion
EFS is defined as failure to achieve MRD-negativity (approximately 0.01% for FACS-MRD, 0.001% for BCR-ABL qPCR), disease relapse, or death from any cause from the date of infusion
Time frame
12 and 24 monthsOther outcomes
1
Duration of B-cell aplasia
B-cell aplasia defined as \<3.0% CD19+ cells/total lymphocytes by peripheral blood flow cytometry.
Time frame
12 months2
Assessment of minimal residual disease by next generation sequencing
MRD by next generation sequencing for clonal B-cell receptor gene rearrangements
Time frame
1, 3, 6, and 12 monthsSponsors and contacts
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Source ClinicalTrials.gov